PMID- 31527313
OWN - NLM
STAT- MEDLINE
DCOM- 20201015
LR  - 20231213
IS  - 2379-3708 (Electronic)
IS  - 2379-3708 (Linking)
VI  - 4
IP  - 20
DP  - 2019 Oct 17
TI  - CD83 orchestrates immunity toward self and non-self in dendritic cells.
LID - 126246 [pii]
LID - 10.1172/jci.insight.126246 [doi]
LID - e126246
AB  - Dendritic cells (DCs) are crucial to balance protective immunity and autoimmune 
      inflammatory processes. Expression of CD83 is a well-established marker for 
      mature DCs, although its physiological role is still not completely understood. 
      Using a DC-specific CD83-conditional KO (CD83DeltaDC) mouse, we provide new insights 
      into the function of CD83 within this cell type. Interestingly, CD83-deficient 
      DCs produced drastically increased IL-2 levels and displayed higher expression of 
      the costimulatory molecules CD25 and OX40L, which causes superior induction of 
      antigen-specific T cell responses and compromises Treg suppressive functions. 
      This also directly translates into accelerated immune responses in vivo. Upon 
      Salmonella typhimurium and Listeria monocytogenes infection, CD83DeltaDC mice cleared 
      both pathogens more efficiently, and CD83-deficient DCs expressed increased IL-12 
      levels after bacterial encounter. Using the experimental autoimmune 
      encephalomyelitis model, autoimmune inflammation was dramatically aggravated in 
      CD83DeltaDC mice while resolution of inflammation was strongly reduced. This 
      phenotype was associated with increased cell influx into the CNS accompanied by 
      elevated Th17 cell numbers. Concomitantly, CD83DeltaDC mice had reduced Treg numbers 
      in peripheral lymphoid organs. In summary, we show that CD83 ablation on DCs 
      results in enhanced immune responses by dysregulating tolerance mechanisms and 
      thereby impairing resolution of inflammation, which also demonstrates high 
      clinical relevance.
FAU - Wild, Andreas B
AU  - Wild AB
AD  - Department of Immune Modulation and.
FAU - Krzyzak, Lena
AU  - Krzyzak L
AD  - Department of Immune Modulation and.
FAU - Peckert, Katrin
AU  - Peckert K
AD  - Department of Immune Modulation and.
FAU - Stich, Lena
AU  - Stich L
AD  - Department of Immune Modulation and.
FAU - Kuhnt, Christine
AU  - Kuhnt C
AD  - Department of Immune Modulation and.
FAU - Butterhof, Alina
AU  - Butterhof A
AD  - Department of Immune Modulation and.
FAU - Seitz, Christine
AU  - Seitz C
AD  - Department of Immune Modulation and.
FAU - Mattner, Jochen
AU  - Mattner J
AD  - Institute of Microbiology - Clinical Microbiology, Immunology and Hygiene, 
      Universitatsklinikum Erlangen and Friedrich-Alexander Universitat 
      Erlangen-Nurnberg, Erlangen, Germany.
FAU - Gruner, Niklas
AU  - Gruner N
AD  - Institute of Microbiology - Clinical Microbiology, Immunology and Hygiene, 
      Universitatsklinikum Erlangen and Friedrich-Alexander Universitat 
      Erlangen-Nurnberg, Erlangen, Germany.
FAU - Gansbauer, Maximilian
AU  - Gansbauer M
AD  - Institute of Microbiology - Clinical Microbiology, Immunology and Hygiene, 
      Universitatsklinikum Erlangen and Friedrich-Alexander Universitat 
      Erlangen-Nurnberg, Erlangen, Germany.
FAU - Purtak, Martin
AU  - Purtak M
AD  - Institute of Microbiology - Clinical Microbiology, Immunology and Hygiene, 
      Universitatsklinikum Erlangen and Friedrich-Alexander Universitat 
      Erlangen-Nurnberg, Erlangen, Germany.
FAU - Soulat, Didier
AU  - Soulat D
AD  - Institute of Microbiology - Clinical Microbiology, Immunology and Hygiene, 
      Universitatsklinikum Erlangen and Friedrich-Alexander Universitat 
      Erlangen-Nurnberg, Erlangen, Germany.
FAU - Winkler, Thomas H
AU  - Winkler TH
AD  - Division of Genetics, Department of Biology, Friedrich-Alexander Universitat 
      Erlangen-Nurnberg, Erlangen, Germany.
FAU - Nitschke, Lars
AU  - Nitschke L
AD  - Division of Genetics, Department of Biology, Friedrich-Alexander Universitat 
      Erlangen-Nurnberg, Erlangen, Germany.
FAU - Zinser, Elisabeth
AU  - Zinser E
AD  - Department of Immune Modulation and.
FAU - Steinkasserer, Alexander
AU  - Steinkasserer A
AD  - Department of Immune Modulation and.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191017
PL  - United States
TA  - JCI Insight
JT  - JCI insight
JID - 101676073
RN  - 0 (Antigens, CD)
RN  - 0 (Immunoglobulins)
RN  - 0 (Membrane Glycoproteins)
SB  - IM
MH  - Animals
MH  - Antigens, CD/genetics/*metabolism
MH  - Brain/immunology/pathology
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Dendritic Cells/*immunology/metabolism
MH  - Encephalomyelitis, Autoimmune, Experimental/*immunology/pathology
MH  - Female
MH  - Humans
MH  - Immune Tolerance
MH  - Immunoglobulins/genetics/*metabolism
MH  - Listeria monocytogenes/immunology
MH  - Listeriosis/*immunology/microbiology
MH  - Membrane Glycoproteins/genetics/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Primary Cell Culture
MH  - Salmonella Infections/*immunology/microbiology
MH  - Salmonella typhimurium/immunology
MH  - T-Lymphocytes, Regulatory/immunology
MH  - Th17 Cells/immunology
MH  - CD83 Antigen
PMC - PMC6824307
OTO - NOTNLM
OT  - Autoimmune diseases
OT  - Autoimmunity
OT  - Dendritic cells
OT  - Inflammation
OT  - Tolerance
COIS- Conflict of interest: The authors have declared that no conflict of interest 
      exists.
EDAT- 2019/09/19 06:00
MHDA- 2020/10/21 06:00
PMCR- 2019/10/17
CRDT- 2019/09/19 06:00
PHST- 2018/11/16 00:00 [received]
PHST- 2019/09/04 00:00 [accepted]
PHST- 2019/09/19 06:00 [pubmed]
PHST- 2020/10/21 06:00 [medline]
PHST- 2019/09/19 06:00 [entrez]
PHST- 2019/10/17 00:00 [pmc-release]
AID - 126246 [pii]
AID - 10.1172/jci.insight.126246 [doi]
PST - epublish
SO  - JCI Insight. 2019 Oct 17;4(20):e126246. doi: 10.1172/jci.insight.126246.